Patent TW-399041-B (TW)
Title: Substituted cyclohexane derivatives, the preparation and the use for treating diseases
Inventor: HEMMERLE HORST
IPC: C07D333/16
Filed: 1993-09-03
Granted: 2000-07-21
Abstract: These are substituted cyclohexane derivatives of the formula I, the preparation process, and the disease-treating compounds. The groups of R1 to R6, X, Y and Z have stated meanings; the preparation processes of these compounds are described. The compounds have valuable pharmacological properties and can therefore be used as pharmaceuticals. Each functional group of the cyclohexane derivate in formula I has the following meaning: R1: CN, COOH, the protected COOH group from COO-C-C1C10-alkyl, COO-C3-C6-cycloalkyl, OO-CH(R7)-O-C1-C4-alkylacyl, COO-phenyl and the like, CO-NH2, CONH-C1-C10-alkyl or CONR8R9 where R7, R8, R9 are defined below, C1-C4-alkylacyl, SO3-C1-C4-alkyl, SO3H, SO2NR8R9, PO(OH)2, PO(OH)(0-C1-C4-alkyl), P0(0-C1-C4-alkyl)2 groups; R2: C1-C10-alkyl (R11)n, O-C1-C10-alkyl(R11)n, C2-C10-alkenyl(R11)n, O-C3-C10-alkenyl(R11)n, C2-C10-alkynyl(R11)n, O-C3-C10-alkynyl(R11)n, S- C1-C10-alkyl(R11)n, S-C3-C10-alkenyl(R11)n, S-C3-C10-alkynyl(R11)n, NH-C1-C10-alkyl(R11)n, NH-C3-C10-alkenyl(R11)n, or NH-C3-C10-alkynyl(R11)n where R12 replaces R11 in various conditions; R3 and R13: the alkylane with 1-10 carbon atoms, the cyclo- alkylane with 3-8 carbon atoms, benzene, naphthane, phenanthane, pyridine, thene, furane pyrimidine, Phthalidylindole, carbazoate, coumarinne, carboimidoate, quinol, piperazine,  tetrazole, triazolyl, quazole, or the tenyl, pyridine, pyrimidine or phenyl heterocyclo derivatives whose aromatic group or hetero-aromatic group could be replaced once or more by the same or different F, Cl, Br, I, OH, CF3, NO2, CN, C1-C4-alkoxide or C1-C4-alkyl, NR8R9, phenyl, pleiadenyl, thenyl, furyl, imidazolyl, pyrimidinyl, O-phenyl or the like; R4,R5 and R6: H, OH, the OH group of the protected alcohol selected from a ester, F, Cl, Br or the meaning stated in R2, while R4, R5 and R6 could be the same or different; R7: C1-C4-alkyl, phenyl or the like; R8 and R9: H, C1-C4-alkyl, C1-C4-alkylacyl, phenyl which could be replaced by F, Cl, Br, I, OH, O-C1-C4-alkyl, CF3, NO2, CN if necessary, while R8 and R9 could be the same or different, or R8 and R9 forms saturated heterocyclic rings with nitrogen atom where the CH2 group could be replaced with O, S, or NR10 if needed; R10: H,C1-C4-alkyl, phenyl or the like; R12:  benzene, naphthane, or phenanthryl, pyridyl, thenyl, furanyl, pyrimidyl, Phthalidylindolyl, carbazoyl, coumarinyl, carboimidoyl, quinolyl, piperazinyl, tetrazolyl, triazolyl, quazolyl, or the tenyl, pyridyl, pyrimidinyl or benzenyl-heterocyclo derivatives whose aromatic group or the hetero-aromatic group could be replaced once or many times by the same or different F, Cl, Br, I, OH, CF3, NO2, CN, C1-C4-alkoxide, C1-C4-alkyl, NR8R9, phenyl, pleiadenyl, thenyl, furyl, imidazolyl, pyrimidinyl, O-phenyl, or the like; X: (CH2)m, -CH=CH, alkynyl , CH2-O-CH2-, -CH2-S-CH2- or Y: (CH2)m, O, S, NR8; Z:(CH2)m, S, O, S-C1-C10-alkyl, O-C1-C10-alkyl, CH=CH, CH=CF, CH=CCl, CH=CBr; CH2-CO, CH2-CHF, -CH2-, CHCl, CH2-CHBr, CH2-CHI, C3-C10-cycloakyl, C3-C10-cycloakylalkenyl where the S, O or N atom can replace 1-3 cyclocarbon atoms,while COOR7, C=C, CH=C, (C1-C4-alkyl), CH=C(CN), CH=C(NR8R9), CH=C(C1-C4-alkylacyl), CH=C(R13), NR8 and when Y is O could form together with R3-Z-C=O- as the one selected from Ala, Arg, Asn, Asp, Cys, Gln, Gly, Mis, Ile, Leu, Lys, Phe, Pro, ser, Thr, Tyr, and the amino acid residue of the protected derivatives from the protecting group from the amino fomic acid carbohydrate, urine derivatives and amino acyl group; n: 0, 1, or 2; m: 0, 1, 2, 3 or 4; and the salts of formula I compound that are physiologically tolerable but does not include the following compounds of formula I: R1 is COOH; R2 is O-C1alkyl (R11)n; n is 0; R3 is a phenyl group with OH substitution at its fourth position; R4 and R5 are is both OH; R6 is hydrogen; X is (CH2)m ; m is 0; Y is oxygen and Z is -CH=CH-.